Graft rejection in the xenogeneic transplantation of mice: diagnosis with in vivo MR imaging using the homing trait of macrophages.
BACKGROUND
To evaluate the feasibility of magnetic resonance (MR) imaging to depict the in vivo recruitment of superparamagnetic iron oxide (SPIO)-labeled macrophages and to diagnose graft rejection in xenogeneic transplantation.


METHODS
We transplanted the trachea of SD rat (xenogeneic) or C3H/HeN mouse (syngeneic) into the left thighs of six male C3H/HeN mice. The SPIO-labeled macrophage was administered through the tail vein 2 days (acute) or 14 days (chronic) after transplantation in each group. The left thighs of the mice were imaged on a 4.7-T MR scanner 24 h after macrophage administration. We evaluated the extent and pattern of the susceptibility effect (macrophage distribution) and compared them in the two groups. The MR findings were then correlated with the histopathologic results. We also measured in both groups the monocyte chemoattractant protein (MCP)-1 level before and 2 days, 2 weeks, and 4 weeks after transplantation.


RESULTS
The band-shaped lower signal intensity (SI) zone was noted around the graft in the acute and chronic phases of xenogeneic group and in the acute phase of syngeneic group, but it was not noted in the chronic phase of syngeneic transplantation. The lower SI zone corresponded to the distribution of SPIO-labeled macrophages on histopathological analyses. On histologic examination, the severe inflammation developed around the xenogeneic graft, but only slightly around the syngeneic graft. MCP-1 was elevated 2 days after transplantation in both groups, but then gradually decreased in the syngeneic group; in xenogenic group, the MCP-1 value decreased by week 2 but then increased by week 4.


CONCLUSIONS
This study demonstrates that the homing of intravenously administered SPIO-labeled macrophages can be monitored on MR imaging and is correlated with the MCP-1 level and the histopathologic findings of the xenograft rejection.
Mun
Han Song
HS
Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, Korea.
Kang
Hee Jung
HJ
Lim
Keun Ho
KH
Sohn
Jin Young
JY
Chang
Hyeujin
H
Lee
Kyoung Geun
KG
Lee
Jin Seong
JS
D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D052203:Ferrosoferric Oxide; D006084:Graft Rejection / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000637:transplantation; D014183:Transplantation, Heterologous; D016042:Transplantation, Heterotopic; D014185:Transplantation, Isogeneic
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D052203:Ferrosoferric Oxide